In the following discussion certain articles and methods will be described for background and introductory purposes. Nothing contained herein is to be construed as an admission of prior art. Applicant expressly reserves the right to demonstrate, where appropriate, that the articles and methods referenced herein do not constitute prior art under the applicable statutory provisions.
Animal models of neurodegenerative disease are excellent tools for studying pathogenesis and therapies including cellular transplantation. Conventionally, there are two approaches to the development of animal models of neurodegenerative disease based on the etiology of the disease. These consist of genetically reproducing the mutations seen in inherited forms of neurodegeneration in animal models, and exposing animals to putative environmental toxins which mimic the clinical manifestations of the disease.
Both of these approaches have drawbacks, however, as neither is representative of the underlying physiological mechanisms for the actual induction of neuronal injury. As neurodegeneration is a multi-faceted event, the presence of a single genetic alteration is rarely enough to mimic the disease, and the exhibition of the neuronal defects may take quite a while, limiting the usefulness of the animal model. With toxins, the onset of the neurodegeneration is usually much quicker, but they often have unwanted (and usually unrelated) side effects that limit their usefulness.
There is thus a need in the art for new, physiologically relevant models of neuronal injury.